Progressive Multifocal LeukoencephalopathyICIPNCT04453917
Dynamics of T Cell Expression of Immune Checkpoint Molecules in Progressive Multifocal Leukoencephalopathy
A study testing Collection of blood and urine, Spinal tap and Brain MRI in people with Progressive Multifocal Leukoencephalopathy, run by University Hospital, Toulouse at 3 sites in France.
Trial summary
Progressive multifocal leukoencephalopathy (PML) is a rare viral infection of the central nervous system (CNS) occurring in immunocompromised patients. Recovery of JC virus (JCV) specific T cell immune responses is the only available therapeutic option. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Progressive Multifocal Leukoencephalopathy
- What is being tested?
- Collection of blood and urine, Spinal tap and Brain MRI
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 3 sitesFrance
- Study dates
- 23 Feb 2021to 12 Jul 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults ≥18 years old
- Informed consent
- Active virological PML : Recent neurological symptoms (< 3 months) with brain MRI lesions suggestive of PML and positive PCR in cerebrospinal fluid for JCV
- Affiliated or benefiting from public health insurance.
Who cannot join
- Non active PML
- Possible PML with negative JCV PCR
- Adults under guardianship or other legal protection, deprived of their liberty by judicial or administrative decision
- Pregnant and/or breastfeeding women
Trial locations and contacts
3 sites in 1 country.
France3 sites
CHU Bordeaux
Bordeaux
CHU Montpellier
Montpellier
CHU de TOULOUSE
Toulouse, 31000
About this study
Progressive multifocal leukoencephalopathy (PML) is a rare viral infection of the central nervous system (CNS) occurring in immunocompromised patients. Recovery of JC virus (JCV) specific T cell immune responses is the only available therapeutic option. JCV may use immune checkpoint inhibitory pathways to evade immune responses. The aim of this project is to determine whether T cell expression of immune checkpoint molecules is correlated to antiviral T cell responses, control of JCV replication and PML outcome. Immune checkpoint blockade by reversing T cell exhaustion may represent a therapeutic perspective for PML.
Read the detailed description
PML is a devastating orphan disease of the CNS due to the reactivation of JCV in immunocompromised patients. Given the lack of drugs controlling JCV replication, initiation of antiretroviral therapy in HIV-infected patients or cessation of immunosuppressive therapies in others, and subsequent recovery of JCV-specific T cell immune responses remains to date the only available therapeutic option. Promoting antiviral immune responses may improve the control of viral replication and the outcome of this severe disease. Immune checkpoint molecules such as PD-1 are inhibitory receptors expressed on T cells that trigger inhibitory signaling pathways, limiting effector immune responses in cancer and chronic infections. Immune checkpoint inhibitory pathways implicated in evading immune responses may be at play in PML. Immune checkpoint blockade using monoclonal antibodies targeting PD-1, by reversing T cell exhaustion, has been suggested as a therapeutic perspective for PML. More insights in the dynamics of immune checkpoint molecules expressed by T cells in PML patients are needed to pave the way for a therapeutic study.
The aim here is to determine whether T cell expression of a broad range of immune checkpoint molecules, and its dynamics, correlates with the generation of antiviral of immune responses, the control of JCV replication and PML outcome.
To this end the investigators will recruit 15 PML patients from 4 teaching hospitals in the South West of France and assess at PML diagnosis and 1, 3 and 6 months after, the expression of immune checkpoint molecules on circulating T cells, ex vivo specific immune responses against a JCV peptide library, JC viral load in cerebrospinal fluid, blood and urine, and clinical and neuroradiological outcomes.
- Being tested
- Collection of blood and urine, Spinal tap, Brain MRI, Neurological evaluation
- Keywords
- Progressive multifocal leukoencephalopathy, Pathophysiology, Immune checkpoint molecules, Immune Checkpoint Inhibitors
- Medical subject headings
- Leukoencephalopathy, Progressive Multifocal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Collection of blood and urineBiological
Collection of blood (47 mL) and urine (5 mL) at PML diagnosis and 1, 3 and 6 months after, for analysis of immune checkpoint molecules expression, detection of antiviral immune responses and virological analyses.
Spinal tapBiological
Spinal tap for monitoring of JC viral load at PML diagnosis and 1, 3 and 6 months after, and collection of CSF (2 mL) for virological analyses.
Brain MRIDiagnostic test
Brain MRI at at PML diagnosis and 3 and 6 months after
Neurological evaluationBiological
Neurological evaluation at PML diagnosis and 1, 3 and 6 months after
| Study group | Role | What they receive |
|---|---|---|
| Patients with active PML | Experimental | Patients with neurological symptoms (< 3 months) with brain MRI lesions suggestive of PML and positive PCR in cerebrospinal fluid for JCV Receives: Biological: Collection of blood and urine; Biological: Spinal tap; Diagnostic Test: Brain MRI; Biological: Neurological evaluation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immune checkpoint molecules
Expression level of a broad panel of immune checkpoint molecules by T cells at PML diagnosis bu flow cytometry
Measured: 1 month
Immune checkpoint molecules
Expression level of a broad panel of immune checkpoint molecules by T cells at PML diagnosis bu flow cytometry
Measured: 3 months
Immune checkpoint molecules
Expression level of a broad panel of immune checkpoint molecules by T cells at PML diagnosis bu flow cytometry
Measured: 6 months
JC viral load
JC viral load in cerebrospinal fluid, blood and urine by ultra-sensitive PCR at PML diagnosis
Measured: 1 month
JC viral load
JC viral load in cerebrospinal fluid, blood and urine by ultra-sensitive PCR at PML diagnosis
Measured: 3 months
JC viral load
JC viral load in cerebrospinal fluid, blood and urine by ultra-sensitive PCR at PML diagnosis
Measured: 6 months
Detection of immune responses against a JCV peptide library
Detection of specific immune responses against a JCV peptide library at PML diagnosis by flow cytometry
Measured: 1 month
Detection of immune responses against a JCV peptide library
Detection of specific immune responses against a JCV peptide library at PML diagnosis by flow cytometry
Measured: 3 months
Detection of immune responses against a JCV peptide library
Detection of specific immune responses against a JCV peptide library at PML diagnosis by flow cytometry
Measured: 6 months
Secondary outcomes (6)
Differential impact of immune checkpoint inhibition
Differential impact of immune checkpoint inhibition in vitro on detection of specific immune responses at PML diagnosis by flow cytometry
Measured: 1 month, 3 months and 6 months
Clinical outcome with Performance status
Clinical outcome using validated scales such as Performance status at PML diagnosis
Measured: 1 month, 3 months and 6 months
Clinical outcome with NIHSS
Clinical outcome using validated scales such as NIHSS (National Institute of Health Stroke Score) at PML diagnosis
Measured: 1 month, 3 months and 6 months
Clinical outcome with Rankin
Clinical outcome using validated scales such as Rankin at PML diagnosis
Measured: 1 month, 3 months and 6 months
Neuroradiological monitoring
Neuroradiological monitoring by brain MRI at PML diagnosis
Measured: 3 months and 6 months
JC virus genotyping
JC virus genotyping in blood, cerebrospinal fluid (CSF) and urine by ultra-sensitive PCR at PML diagnosis
Measured: 1 month, 3 months and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2020
- Study start23 Feb 2021
- Primary completion12 Jul 2024
- Study completion12 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Progressive Multifocal LeukoencephalopathyStudies of the same condition, open and under way.
- More trials run by University Hospital, ToulouseThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Patients with neurological symptoms (\< 3 months) with brain MRI lesions suggestive of PML and positive PCR in cerebrospinal fluid for JCV
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Guillaume MARTIN-BLONDEL, Principal investigator, University Hospital, Toulouse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04453917
- Sponsor's protocol ID
- RC31/19/0506
- Acronym
- ICIP
- Status last verified
- Dec 2025
- First submitted
- 3 Jun 2020
- Last updated
- 31 Dec 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dynamics of T Cell Expression of Immune Checkpoint Molecules in Progressive Multifocal Leukoencephalopathy
- ClinicalTrials.gov ID
- NCT04453917
- Acronym / sponsor ID
- ICIP / RC31/19/0506
- Keywords
- Progressive multifocal leukoencephalopathy, Pathophysiology, Immune checkpoint molecules, Immune Checkpoint Inhibitors
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- University Hospital, ToulouseUniversity, hospital or other
- Study start
- 23 Feb 2021 (actual)
- Primary completion
- 12 Jul 2024 (actual)
- Study completion
- 12 Jul 2024 (actual)
- First posted
- 1 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Progressive multifocal leukoencephalopathy (PML) is a rare viral infection of the central nervous system (CNS) occurring in immunocompromised patients. Recovery of JC virus (JCV) specific T cell immune responses is the only available therapeutic option. JCV may use immune checkpoint inhibitory pathways to evade immune responses. The aim of this project is to determine whether T cell expression of immune checkpoint molecules is correlated to antiviral T cell responses, control of JCV replication and PML outcome. Immune checkpoint blockade by reversing T cell exhaustion may represent a therapeutic perspective for PML.
Detailed description
PML is a devastating orphan disease of the CNS due to the reactivation of JCV in immunocompromised patients. Given the lack of drugs controlling JCV replication, initiation of antiretroviral therapy in HIV-infected patients or cessation of immunosuppressive therapies in others, and subsequent recovery of JCV-specific T cell immune responses remains to date the only available therapeutic option. Promoting antiviral immune responses may improve the control of viral replication and the outcome of this severe disease. Immune checkpoint molecules such as PD-1 are inhibitory receptors expressed on T cells that trigger inhibitory signaling pathways, limiting effector immune responses in cancer and chronic infections. Immune checkpoint inhibitory pathways implicated in evading immune responses may be at play in PML. Immune checkpoint blockade using monoclonal antibodies targeting PD-1, by reversing T cell exhaustion, has been suggested as a therapeutic perspective for PML. More insights in the dynamics of immune checkpoint molecules expressed by T cells in PML patients are needed to pave the way for a therapeutic study.
The aim here is to determine whether T cell expression of a broad range of immune checkpoint molecules, and its dynamics, correlates with the generation of antiviral of immune responses, the control of JCV replication and PML outcome.
To this end the investigators will recruit 15 PML patients from 4 teaching hospitals in the South West of France and assess at PML diagnosis and 1, 3 and 6 months after, the expression of immune checkpoint molecules on circulating T cells, ex vivo specific immune responses against a JCV peptide library, JC viral load in cerebrospinal fluid, blood and urine, and clinical and neuroradiological outcomes.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patients with neurological symptoms (< 3 months) with brain MRI lesions suggestive of PML and positive PCR in cerebrospinal fluid for JCV
| Arm | Type | Receives |
|---|---|---|
| Patients with active PML | Experimental | Biological: Collection of blood and urine, Biological: Spinal tap, Diagnostic Test: Brain MRI, Biological: Neurological evaluationPatients with neurological symptoms (< 3 months) with brain MRI lesions suggestive of PML and positive PCR in cerebrospinal fluid for JCV |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adults ≥18 years old
- Informed consent
- Active virological PML : Recent neurological symptoms (< 3 months) with brain MRI lesions suggestive of PML and positive PCR in cerebrospinal fluid for JCV
- Affiliated or benefiting from public health insurance.
Key exclusion criteria (4 listed)
- Non active PML
- Possible PML with negative JCV PCR
- Adults under guardianship or other legal protection, deprived of their liberty by judicial or administrative decision
- Pregnant and/or breastfeeding women
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Collection of blood and urineCollection of blood (47 mL) and urine (5 mL) at PML diagnosis and 1, 3 and 6 months after, for analysis of immune checkpoint molecules expression, detection of antiviral immune responses and virological analyses. | Biological | Patients with active PML |
| Spinal tapSpinal tap for monitoring of JC viral load at PML diagnosis and 1, 3 and 6 months after, and collection of CSF (2 mL) for virological analyses. | Biological | Patients with active PML |
| Brain MRIBrain MRI at at PML diagnosis and 3 and 6 months after | Diagnostic test | Patients with active PML |
| Neurological evaluationNeurological evaluation at PML diagnosis and 1, 3 and 6 months after | Biological | Patients with active PML |
Primary outcome
Immune checkpoint molecules
Time frame: 1 month
Expression level of a broad panel of immune checkpoint molecules by T cells at PML diagnosis bu flow cytometry
Immune checkpoint molecules
Time frame: 3 months
Expression level of a broad panel of immune checkpoint molecules by T cells at PML diagnosis bu flow cytometry
Immune checkpoint molecules
Time frame: 6 months
Expression level of a broad panel of immune checkpoint molecules by T cells at PML diagnosis bu flow cytometry
JC viral load
Time frame: 1 month
JC viral load in cerebrospinal fluid, blood and urine by ultra-sensitive PCR at PML diagnosis
JC viral load
Time frame: 3 months
JC viral load in cerebrospinal fluid, blood and urine by ultra-sensitive PCR at PML diagnosis
JC viral load
Time frame: 6 months
JC viral load in cerebrospinal fluid, blood and urine by ultra-sensitive PCR at PML diagnosis
Detection of immune responses against a JCV peptide library
Time frame: 1 month
Detection of specific immune responses against a JCV peptide library at PML diagnosis by flow cytometry
Detection of immune responses against a JCV peptide library
Time frame: 3 months
Detection of specific immune responses against a JCV peptide library at PML diagnosis by flow cytometry
Detection of immune responses against a JCV peptide library
Time frame: 6 months
Detection of specific immune responses against a JCV peptide library at PML diagnosis by flow cytometry
6 secondary outcomes
Differential impact of immune checkpoint inhibition
Time frame: 1 month, 3 months and 6 months
Clinical outcome with Performance status
Time frame: 1 month, 3 months and 6 months
Clinical outcome with NIHSS
Time frame: 1 month, 3 months and 6 months
Clinical outcome with Rankin
Time frame: 1 month, 3 months and 6 months
Neuroradiological monitoring
Time frame: 3 months and 6 months
JC virus genotyping
Time frame: 1 month, 3 months and 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Guillaume MARTIN-BLONDEL principal investigator
University Hospital, Toulouse
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Collection of blood and urine, Spinal tap and Brain MRI in people with Progressive Multifocal Leukoencephalopathy, run by University Hospital, Toulouse at 3 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Immune checkpoint molecules (time frame: 1 month). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Dec 2025.